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TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner

IL-10 producing B cells (B10 cells) play an important immunoregulatory role in various autoimmune and infection conditions. However, the factors that regulate their development and maintenance are incompletely understood. Recently, we and others have established a requirement for TLR7 in promoting a...

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Autores principales: Chodisetti, Sathi Babu, Fike, Adam J., Domeier, Phillip P., Choi, Nicholas M., Soni, Chetna, Rahman, Ziaur S. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399053/
https://www.ncbi.nlm.nih.gov/pubmed/32849556
http://dx.doi.org/10.3389/fimmu.2020.01632
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author Chodisetti, Sathi Babu
Fike, Adam J.
Domeier, Phillip P.
Choi, Nicholas M.
Soni, Chetna
Rahman, Ziaur S. M.
author_facet Chodisetti, Sathi Babu
Fike, Adam J.
Domeier, Phillip P.
Choi, Nicholas M.
Soni, Chetna
Rahman, Ziaur S. M.
author_sort Chodisetti, Sathi Babu
collection PubMed
description IL-10 producing B cells (B10 cells) play an important immunoregulatory role in various autoimmune and infection conditions. However, the factors that regulate their development and maintenance are incompletely understood. Recently, we and others have established a requirement for TLR7 in promoting autoimmune antibody forming cell (AFC) and germinal center (GC) responses. Here we report an important additional role of TLR7 in the negative regulation of B10 cell development. TLR7 overexpression or overstimulation promoted the reduction of B10 cells whereas TLR7 deficiency rescued these cells in both non-autoimmune and autoimmune-prone mice. TLR7 expression was further inversely correlated with B cell-dependent IL-10 production and its inhibition of CD4 T cell proliferation and IFNγ production in an in vitro B cell and T cell co-culture system. Further, B10 cells displayed elevated TLR7, IFNγR, and STAT1 expression compared to non-B10 cells. Interestingly, deficiency of IFNγR in TLR7 overexpressing lupus-prone mice rescued B10 cells from TLR7-mediated reduction. Finally, B cell intrinsic deletion of IFNγR was sufficient to restore B10 cells in the spleens of TLR7-promoted autoimmune mouse model. In conclusion, our findings demonstrate a novel role for the IFNγR-STAT1 pathway in TLR7-mediated negative regulation of B10 cell development.
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spelling pubmed-73990532020-08-25 TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner Chodisetti, Sathi Babu Fike, Adam J. Domeier, Phillip P. Choi, Nicholas M. Soni, Chetna Rahman, Ziaur S. M. Front Immunol Immunology IL-10 producing B cells (B10 cells) play an important immunoregulatory role in various autoimmune and infection conditions. However, the factors that regulate their development and maintenance are incompletely understood. Recently, we and others have established a requirement for TLR7 in promoting autoimmune antibody forming cell (AFC) and germinal center (GC) responses. Here we report an important additional role of TLR7 in the negative regulation of B10 cell development. TLR7 overexpression or overstimulation promoted the reduction of B10 cells whereas TLR7 deficiency rescued these cells in both non-autoimmune and autoimmune-prone mice. TLR7 expression was further inversely correlated with B cell-dependent IL-10 production and its inhibition of CD4 T cell proliferation and IFNγ production in an in vitro B cell and T cell co-culture system. Further, B10 cells displayed elevated TLR7, IFNγR, and STAT1 expression compared to non-B10 cells. Interestingly, deficiency of IFNγR in TLR7 overexpressing lupus-prone mice rescued B10 cells from TLR7-mediated reduction. Finally, B cell intrinsic deletion of IFNγR was sufficient to restore B10 cells in the spleens of TLR7-promoted autoimmune mouse model. In conclusion, our findings demonstrate a novel role for the IFNγR-STAT1 pathway in TLR7-mediated negative regulation of B10 cell development. Frontiers Media S.A. 2020-07-28 /pmc/articles/PMC7399053/ /pubmed/32849556 http://dx.doi.org/10.3389/fimmu.2020.01632 Text en Copyright © 2020 Chodisetti, Fike, Domeier, Choi, Soni and Rahman. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chodisetti, Sathi Babu
Fike, Adam J.
Domeier, Phillip P.
Choi, Nicholas M.
Soni, Chetna
Rahman, Ziaur S. M.
TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner
title TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner
title_full TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner
title_fullStr TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner
title_full_unstemmed TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner
title_short TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner
title_sort tlr7 negatively regulates b10 cells predominantly in an ifnγ signaling dependent manner
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399053/
https://www.ncbi.nlm.nih.gov/pubmed/32849556
http://dx.doi.org/10.3389/fimmu.2020.01632
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